Researchers find potential new treatment approach for pancreatic cancer
Scientists from CMFT - part of Manchester Cancer Research Centre
- believe they have discovered a new way to make chemotherapy
treatment more effective for pancreatic cancer patients.
Pancreatic cancer is an aggressive cancer with poor prognosis
and limited treatment options and is highly resistant to
chemotherapy and radiotherapy.
But researchers believe they have found an effective strategy
for selectively killing pancreatic cancer while sparing healthy
cells which could make treatment more effective.
Dr Jason Bruce, from the Physiological Systems and Disease
Research Group, who led the research, said: "Pancreatic cancer is
one of the most aggressive and deadly cancers. Most patients
develop symptoms after the tumour has spread to other organs. To
make things worse, pancreatic cancer is highly resistant to
chemotherapy and radiotherapy. Clearly a radical new approach to
treatment is urgently required. We wanted to understand how the
switch in energy supply in cancer cells might help them
The research, published in The Journal of Biological Chemistry
this month, found pancreatic cancer cells may have their own
specialised energy supply that maintains calcium levels and keeps
cancer cells alive.
Maintaining a low concentration of calcium within cells is vital
to their survival and this is achieved by calcium pumps on the
This calcium pump, known as PMCA, is fuelled using ATP - the key
energy currency for many cellular processes.
All cells generate energy from nutrients using two major
biochemical energy "factories", mitochondria and glycolysis.
Mitochondria generate approximately 90% of the cells' energy in
normal healthy cells. However, in pancreatic cancer cells there is
a shift towards glycolysis as the major energy source. It is
thought that the calcium pump may have its own supply of glycolytic
ATP, and it is this fuel supply that gives cancer cells a survival
advantage over normal cells.
Scientists used cells taken from human tumours and looked at the
effect of blocking each of these two energy sources in turn.
Their study, funded by the Biotechnology and Biological Sciences
Research Council (BBSRC), Central Manchester University Hospitals
NHS Foundation Trust (CMFT)/National Institute of Health Research
(NIHR) Manchester Biomedical Research Centre and AstraZeneca, shows
that blocking mitochondrial metabolism had no effect. However, when
they blocked glycolysis, they saw a reduced supply of ATP which
inhibited the calcium pump, resulting in a toxic calcium overload
and ultimately cell death.
Dr Bruce added: "It looks like glycolysis is the key process in
providing ATP fuel for the calcium pump in pancreatic cancer cells.
Although an important strategy for cell survival, it may also be
their major weakness.
"Designing drugs to cut off this supply to the calcium pumps
might be an effective strategy for selectively killing cancer cells
while sparing normal cells within the pancreas."
Maggie Blanks, CEO of the national charity, the Pancreatic
Cancer Research Fund said: "These findings will certainly of great
interest to the pancreatic cancer research community and we'd be
keen to see how this approach progresses. Finding weaknesses that
can be exploited in this highly aggressive cancer is paramount, so
we want to congratulate the Manchester team for their
For further information, please contact Alison Barbuti, Media
Alison Barbuti | Media Relations Officer | Faculty of Medical
and Human Sciences |The University of Manchester - part of
Manchester Cancer Research Centre
Tel. +44 (0)161 275 8383 Internal: 58383 | Mobile 07887 561 318
Notes to Editors
Glycolytic ATP Fuels the Plasma Membrane Calcium Pump Critical
for Pancreatic Cancer Cell Survival
The Journal of Biological Chemistry, Vol. 288, Issue 50,
36007-36019, December 13, 2013
Andrew D. James; Oihane Erice; Jason I. E. Bruce
University of Manchester
This work was supported by a Biotechnology and Biological
Sciences Research Council (BBSRC) New Investigator Grant (to Jason
Bruce) and a Central Manchester University Hospitals NHS Foundation
Trust (CMFT)/National Institutes of Health Research (NIHR)
Manchester Biomedical Research Centre (BRC) pump priming fund (to
Ajith Siriwardena and Jason Bruce). Andrew James was supported by
BBSRC and AstraZeneca CASE Ph.D. studentship.
Information about pancreatic cancer:
Has the worst survival rate of any common cancer - only 3 in
every 100 people diagnosed will live beyond 5 years.
It is a highly aggressive cancer, but symptoms are vague and
generally only appear in the later stages of the disease.
With no early diagnostic test, only 10% of patients are
diagnosed early enough for surgery, currently the only potentially
Despite being the UK's 5th biggest cancer killer, pancreatic
cancer receives less than 2% of national research funding.
Some 8,500 people are diagnosed every year.
Manchester Cancer Research Centre
The Manchester Cancer Research Centre (MCRC) is a partnership
founded by The University of Manchester, including the Paterson
Institute for Cancer Research, The Christie NHS Foundation Trust
and Cancer Research UK. The MCRC brings together the expertise,
ambition and resources of its partner organisations in the fields
of cancer treatment and clinical research and provides outstanding
facilities where researchers and clinicians can work closely
together. The aim of the MCRC is to improve understanding of how
cancer develops, in order to translate basic and clinical research
into new diagnostic tests and treatments that benefit cancer
patients. More information is available at: www.manchester.ac.uk/mcrc
The Manchester Biomedical Research Centre is a partnership
between Central Manchester University Hospitals NHS Foundation
Trust and The University of Manchester, with the aim of improving
health through science. www.manchesterbrc.org